Capsules containing pharmaceutical preparations are widely used in the treatment and diagnosis of diseases. The capsules may be administered orally or are used in specific medical devices such as powder inhalers. As a rule, the capsules consist of two parts, a capsule body (body) and a capsule cap (cap) which are pushed telescopically into one another. However, multi-sectional capsules are also known. The capsules generally consist of gelatine, particularly hard gelatine. For some special purposes, the capsules are occasionally made of water-soluble plastics which are easily digested by the patient so that when administered orally the active substance is released in certain sections of the gastrointestinal tract. Some examples of various capsule materials are give hereinafter.
EP 0460921 describes capsules consisting of chitosan and starch, powdered cereal, oligosaccharides, methacrylic acid-methylacrylate, methacrylic acid-ethylacrylate, hydroxypropylmethylcellulose acetate, succinate, or phthalate. The capsule material is characterized in that the contents are only released in the large bowel.
GB 938828 discloses capsules for radioactive substances for therapeutic or diagnostic use. The capsules consist of water-soluble gelatine, methylcellulose, polyvinylalcohol, or water-soluble non-toxic thermoplasts.
EP 0312760 describes a method of sealing hard gelatine or starch capsules with a specific sealing agent. The seam in the capsules may be displaced from the central plane of the longitudinal axis of the capsule.
DE 3430764 discloses another method of sealing hard gelatine capsules. In this method the capsules are first filled and the two capsule halves are fitted together telescopically. Then, by lifting the cap relative to the body of the capsule, a contact zone is exposed on the capsule body, but the capsule must not be opened. In a subsequent step, the contact zone is then made “tacky” so that the cap can then be pushed back onto its original position and brought into contact with the contact zone. This process requires high precision when carrying it out particularly as it is important to avoid deforming the capsule when the cap is pushed back onto the capsule body which has been made tacky by heating and thereby been made more prone to deformation. Page 32 of the application states that tools with no tolerances or play of any kind are needed in order to hold and guide the capsule sections.
U.S. Pat. No. 4,991,377 discloses another process for sealing keratin or gelatine capsules. In this process, the sealed capsule which consists of two telescopically connected sections is treated with hot air at its weld seam. During the process, the lower part of the capsule rests on a holder. The patent specification does not give any hint as to how to avoid deformation of the capsules softened by the blast of heat nor how to avoid heating or carbonization of other parts of the capsule outside the seam zone. Nor is there any mention of how the quality of the contents of the capsule is affected by the heat produced by the welding.
WO 00/07572 discloses capsules for inhalers of the kind according to the invention which consist of indigestible plastic. We hereby refer expressly to this patent document and the object disclosed therein. The capsules described therein are sealed analogously to standard commercial hard gelatine capsules, i.e., the capsule cap is placed telescopically on the capsule body. The seam which is necessarily produced between the cap and the body may optionally be welded, glued or banded to reduce the steam permeability. Alternatively, the entire cap may be covered with a continuous protective film or the gap in the seam may be filled with a filler. There are no details of the methods of sealing the cap, particularly no mention of any welding processes.
Various thermal welding methods are known from the prior art for welding plastic materials. These include ultrasonic welding, hot plate and hot tool welding, hot gas welding, rotary welding, high frequency voltage welding, or induction welding.
By contrast, processes of this kind for sealing plastic capsules for medicinal inhalers, which are subject to certain limiting conditions with regard to their use, are not known.
It has now been found that these welding processes cannot readily be transferred to the welding of the capsule halves described in WO 00/07572.
The limiting conditions mentioned above, which prevent the simple transfer of the methods known from the prior art to capsules for inhalation, include the fact, for example, that the capsules are filled with a pharmaceutical formulation the pharmaceutical quality of which must not be impaired during the welding process.
Another condition is laid down by the dimensions and thickness of the capsules to be welded, particularly the thin walls of such capsules. This is necessary to allow the capsule to be used in a standard commercial inhaler analogously to the hard gelatine capsules currently in common use. In fact, it has to be capable of being opened easily. If the conventional methods are applied to such a capsule, holes will rapidly be burnt into the capsule during the welding process, particularly in those parts of the capsule which are outside the area being welded. This area where the seam is to be formed is naturally in a region where the walls of the two parts to be joined together overlap. Next to this area there are parts where there is no such overlap. In these parts, the capsule can more easily be damaged by the welding process. There is also the danger that if the capsule walls are too thick, any weld seam at the junction will not be properly sealed.